Nanoparticle-oligonucleotide hybrid structures and methods of use thereof

Abstract

The invention relates to hybrid structures comprising an amphiphilic nucleic acid-block co-polymer assembly on the exterior and a nanoparticle core, and methods of use thereof.

What is claimed is: 
     
       1. A nanoparticle-nucleic acid hybrid structure, comprising a high density oligonucleotide-amphiphilic block co-polymer exterior assembly and a hydrophobic nanoparticle core. 
     
     
       2. The hybrid structure of  claim 1 , wherein said nucleic acid is DNA, RNA, artificial nucleic acids or a combination thereof. 
     
     
       3. The hybrid structure of  claim 1 , wherein said oligonucleotide is an oligonucleotide ranging in size from 5-100 base pairs. 
     
     
       4. The hybrid structure of  claim 1 , wherein said block-copolymers comprise an oligonucleotide block and a polystyrene block. 
     
     
       5. The hybrid structure of  claim 1 , wherein said structure enables detection of single base mismatches from complementary strands. 
     
     
       6. The hybrid structure of  claim 1 , wherein said structure enhances its stability in water. 
     
     
       7. The hybrid structure of  claim 6 , wherein said nanoparticle is an iron oxide magnetic particle. 
     
     
       8. The hybrid structure of  claim 1 , wherein said nanoparticle is a gold nanoparticle, a magnetic nanoparticle, a semiconductor nanoparticle, an insulator nanoparticle, a metallic nanoparticle, a carbon black particle, a quantum dot or any combination thereof. 
     
     
       9. The hybrid structure of  claim 8 , wherein said iron oxide magnetic particle is functionalized via ligand exchange with alpha-carboxyl polystyrene. 
     
     
       10. The hybrid structure of  claim 1 , wherein the nanoparticle is a magnetic nanoparticle selected from the group consisting of a metal nanoparticle, a metal oxide nanoparticle, a metalloid nanoparticle, a metalloid oxide nanoparticle, or a combination thereof. 
     
     
       11. The hybrid structure of  claim 1 , wherein said nanoparticle ranges in size from 1-1000 nanometers in diameter. 
     
     
       12. The hybrid structure of  claim 1 , wherein said structure enables selective nucleic acid binding to complementary nucleic acid under low salt concentration. 
     
     
       13. The hybrid structure of  claim 1 , wherein said structure enhances the binding affinity to a nucleic acid complementary to said nucleic acid. 
     
     
       14. The hybrid structure of  claim 1 , wherein said nucleic acid on said structure selectively binds to a complementary nucleic acid by detecting mismatches between said nucleic acid on said hybrid structure and a nucleic acid contacted by said hybrid structure. 
     
     
       15. The hybrid structure of  claim 14 , wherein said fluorescence molecule is a fluorescein, a cyanine dye, or a combination thereof. 
     
     
       16. The hybrid structure of  claim 1 , wherein said structure further comprises a fluorescence molecule. 
     
     
       17. A method for facilitating self-assembly of a nanoparticle-nucleic acid hybrid structure, comprising a high density oligonucleotide-amphiphilic block co-polymer exterior assembly and a hydrophobic nanoparticle core, the method comprising the step of mixing a pre-determined amount of nucleic acid amphiphilic block-copolymer with a pre-determined amount of nanoparticles to facilitate the self-assembly of said hybrid structure. 
     
     
       18. A method for transfecting a cell with a nucleic acid, comprising contacting a cell with a nanoparticle-nucleic acid hybrid structure, comprising a high density oligonucleotide-amphiphilic block co-polymer exterior assembly and a hydrophobic nanoparticle core. 
     
     
       19. The method of  claim 18 , wherein the hybrid structure further comprises a targeting agent. 
     
     
       20. The method of  claim 19 , further comprising contacting the cell with the hybrid structure in the presence of an applied magnetic field. 
     
     
       21. A method of separating nucleic acid molecules, said method comprising the step of contacting a nucleic said molecule complementary to said nucleic acid molecule comprised by a nanoparticle-nucleic acid hybrid structure, comprising a high density oligonucleotide-amphiphilic block co-polymer exterior assembly and a hydrophobic nanoparticle core. 
     
     
       22. The method of  claim 21 , further comprising the step of contacting the nucleic acid with the hybrid structure in the presence of an applied magnetic field. 
     
     
       23. A method for imaging a cell, comprising: contacting a cell with a nanoparticle-nucleic acid hybrid structure to provide a labeled cell, wherein said nanoparticle-nucleic acid hybrid structure comprises a high density oligonucleotide-amphiphilic block co-polymer exterior assembly and a hydrophobic nanoparticle core; and imaging the labeled cell. 
     
     
       24. The method of  claim 23 , wherein imaging comprises optical imaging, wherein said optical imaging is fluorescence imaging, scattering imaging, colorimetric imaging, electron microscopy imaging, or magnetic resonance imaging. 
     
     
       25. The method of  claim 23 , wherein the hybrid structure comprises a quantum dot and the imaging comprises fluorescent imaging. 
     
     
       26. The method of  claim 23 , wherein the hybrid structure comprises a magnetic nanoparticle and the imaging comprises magnetic resonance imaging. 
     
     
       27. The method of  claim 23 , wherein the hybrid structure further comprises a targeting agent. 
     
     
       28. A method for detecting a complementary nucleic acid sequence with high selectivity, the method comprising the step of utilizing a nanoparticle-nucleic acid hybrid structure in an assay to selectively detect said complementary nucleic acid, wherein said nanoparticle-nucleic acid hybrid structure comprises a high density oligonucleotide-amphiphilic block co-polymer exterior assembly and a hydrophobic nanoparticle core. 
     
     
       29. The method of  claim 28 , wherein said selection process is a nucleic acid binding assay that detects binding of said nucleic acid to a complementary nucleic acid. 
     
     
       30. The method of  claim 28 , wherein said hybrid structure enables detection of a complementary nucleic acid under low salt concentrations. 
     
     
       31. The method of  claim 28 , wherein said complementary nucleic acid sequence is a sequence of a gene. 
     
     
       32. A method for delivering a composition to a cell, the method comprising: contacting said cell with a nanoparticle-nucleic acid hybrid structure that comprises a high density oligonucleotide-amphiphilic block co-polymer exterior assembly and a hydrophobic nanoparticle core. 
     
     
       33. A nanoparticle-nucleic acid hybrid structure, comprising a high density oligonucleotide-amphiphilic block co-polymer exterior assembly and a hydrophobic nanoparticle core, wherein said hybrid structure comprises more oligonucleotides than a structure having said nanoparticle alone without said oligonucleotide-amphiphilic block co-polymer exterior assembly.